WJV  Vol.3 No.2 , May 2013
Proteoliposome and Polysaccharide-Based Meningococcal Vaccine Are Immunogenic in Infants and Toddlers and Primes for Memory against Serogroup C Polysaccharide
Abstract: Neisseria meningitidis capsular polysaccharides are the main target of the protective immune response against bacterial meningitis. They are thymus-independent type 2 (TI-2) antigens that are poorly immunogenic and not protective in young children, and their administration may impair subsequent challenge with the same polysaccharide. These problems have been addressed using three different vaccines consisting of 1) polysaccharide alone, 2) polysaccharide covalently conjugated to a carrier protein, and 3) polysaccharide with Proteoliposome (PL) adsorbed onto Al(OH)3. VA-MENGOC-BC? is one of the third types of vaccine. It contains PL (detergent-extracted external membrane proteins forming vesicles) and polysaccharide (Ps) from N. meningitidis serogroups B and C (PsC), respectively. Nevertheless, there is a concern that to overcome the TI-2 nature of Ps the covalently conjugation to a carrier is mandatory. Therefore, we evaluated the immune response induced by VA-MENGOC-BC? in infants and toddlers in order to determine whether it stimulates the response against the PsC. High IgG anti PsC and anti PL responses were seen following the administration of two doses in infants and toddlers, after a 3rd dose in pre-teenagers, and after confirmed carrier stages in young adults. The anti PL IgG response persisted longer than anti PsC IgG response and IgM response against both antigens was maintained. An IgG1 anti PL response predominated, as well as IgG4 > IgG3 > IgG1 anti PsC responses. These results suggest that non-covalent incorporation of PsC onto Al(OH)3 containing PL as adjuvant is immunogenic, primes for memory, and induces long-lasting specific antibody response. The improved PsC immunogenicity of this vaccine may be due to the preferential and potent Th1 response induced in mice and human by the PL as adjuvant.
Cite this paper: O. Pérez, B. Romeu, J. Campo, C. Zayas and M. Lastre, "Proteoliposome and Polysaccharide-Based Meningococcal Vaccine Are Immunogenic in Infants and Toddlers and Primes for Memory against Serogroup C Polysaccharide," World Journal of Vaccines, Vol. 3 No. 2, 2013, pp. 77-87. doi: 10.4236/wjv.2013.32012.

[1]   P. Richmond, E. Kaczmarski, R. Borrow, J. Findlow, S. Clark, R. McCann, et al., “Meningococcal C Polysaccharide Vaccine Induces Hyporesponsiveness in Adults That Is Overcome by Conjugate Vaccine,” Journal of Infectious Diseases, Vol. 181, No. 2, 2000, pp. 761-764. doi:10.1086/315284

[2]   J. Southern, S. Deane, L. Ashton, R. Borrow, D. Goldblatt, N. Andrews, et al., “Effects of Prior Polysaccharide Vaccination on Magnitude, Duration, and Quality of Immune Responses to and Safety Profile of a Meningococcal Serogroup C Tetanus Toxoid Conjugate Vaccination in Adults,” Clinical and Diagnostic Laboratory Immunology, Vol. 11, No. 6, 2004, pp. 1100-1104.

[3]   A. Leach, P. A. Twumasi, S. Kunah, W. S. Banya, S. Jaffar, B. D. Forrest, et al., “Induction of Immunologic Memory in Gambian Children by Vaccination in Infancy with a Group A Oplus Group C Meningococcal Polysaccharide-Protein Conjugate Vaccine,” Journal of Infectious Diseases, Vol. 175, No. 1, 1997, pp. 200-204. doi:10.1093/infdis/175.1.200

[4]   A. L. Reingold, C. V. Broome, A. W. Hightower, G. W. Ajello, G. A. Bolan, C. Adamsbaum, et al., “Age-Specific Differences in Duration of Clinical Protection after Vaccination with Meningococcal Polysaccharide A Vaccine,” Lancet, Vol. 2, No. 8447, 1985, pp. 114-118. doi:10.1016/S0140-6736(85)90224-7

[5]   S. J. Cessay, S. J. Allen, A. Menon, J. E. Todd, K. Cham, G. M. Carlone, et al., “Decline in Meningococcal Antibody Levels in African Children 5 Years after Vaccination and the Lack of an Effect of Booster Immunization,” Journal of Infectious Diseases, Vol. 167, No. 5, 1993, pp. 1212-1216. doi:10.1093/infdis/167.5.1212

[6]   J. Eskola and H. Kayhty, “Ten Years’ Experience with Haemophilus influenzae Type b (Hib) Conjugate Vaccines in Finland,” Reviews in Medical Microbiology, Vol. 7, No. 4, 1996, pp. 179-231. doi:10.1097/00013542-199610000-00005

[7]   H. J. Jennings and C. Lugowski, “Immunochemestry of Groups A, B, and C Neningococcal Polysaccharide-Tetanous Toxoid Conjugates,” The Journal of Immunology, Vol. 127, 1981, pp. 1011-1018.

[8]   P. C. Richmond, R. Borrow, E. Miller, S. Clark, F. Sadler, A. Fox, et al., “Meningococcal Serogroup C Conjugate Vaccine Is Immunogenic in Infancy and Primes for Memory,” Journal of Infectious Diseases, Vol. 179, No. 6, 1999, pp. 1569-1572. doi:10.1086/314753

[9]   J. J. Mond, A. Lees and C. M. Snapper, “T Cell-Independent Antigens Type 2,” Annual Review of Immunology, Vol. 13, 1995, pp. 655-692. doi:10.1146/annurev.iy.13.040195.003255

[10]   F. E.Wyle, M. S. Artenslein, R. L. Branck, E. C. Tramont, D. L. Kasper, P. L. Altieri, et al., “Immunological Response in Man to Group B Meningococcal Polysaccharide Vaccines,” Journal of Infectious Diseases, Vol. 126, No. 5, 1972, pp. 514-522. doi:10.1093/infdis/126.5.514

[11]   J. Holst, D. Martin, R. Arnold, C. C. Huergo, P. Oster, J. O’Hallahan, et al., “Properties and Clinical Performance of Vaccines Containing Outer Membrane Vesicles from Neisseria meningitides,” Vaccine, Vol. 27, No. 2, 2009, pp. B3-B12. doi:10.1016/j.vaccine.2009.04.071

[12]   C. Huergo, G. Sierra, M. M. Gutiérrez, G. Bisset, L. G. Garcia, G. Puentes, et al., European Patent 885900077.8, 1988.

[13]   C. C. Huergo, V. G. Sierra, M. M. Gutiérrez, G. Bisset, L. G. Garcia, G. Puentes, et al., United States Patent N. 5597572, 1997.

[14]   G. V. Sierra, C. H. Campa and M. Varcárcel, “Vaccine against Group B Neisseria meningitidis: Protection Trial and Mass Vaccination Results in Cuba,” NIPH Annals, Vol. 14, No. 2, 1991, pp. 195-210.

[15]   O. Pérez, M. Lastre, J. Lapinet, G. Bracho, M. Díaz, C. Zayas, et al., “Immune Response Induction and New Effector Mechanisms Possibly Involved in Protection Conferred by the Cuban Anti-Meningococcal BC Vaccine,” Infection and Immunity, Vol. 69, No. 7, 2001, pp. 4502-4508. doi:10.1128/IAI.69.7.4502-4508.2001

[16]   “Meningococcal Disease in Universitary Students,” CDR Wkly, Vol. 8, No. 1, 1998, pp. 49-52.

[17]   N. MacDonald, S. A. Halperin, B. J. Law, B. Forrest, L. E. Danzig, and D. M. Granoff, “Induction of Immunologic Memory by Conjugated vs Plain Meningococcal C Polysaccharide Vaccine in Toddlers,” JAMA, Vol. 280, No. 19, 1998, pp. 1685-1689. doi:10.1001/jama.280.19.1685

[18]   N. E. MacDonald, S. A. Heparin, B. J. Law, L. E. Danzig and D. M. Granoff, “Can Meningococcal C Conjugate Vaccine Overcome Immune Hyporesponsiveness Induced by Previous Administration of Plain Polysaccharide Vaccine?” JAMA, Vol. 283, No. 14, 2000, pp. 1826-1827. doi:10.1001/jama.283.14.1826

[19]   G. Reed and M. A. Galindo, “Cuba’s National Immunization Program,” MEDICC Review, Vol. 9, No. 1, 2007, pp. 5-7.

[20]   “Normas para la Vacuna Polisacáridas Meningococcicas,” Informe OMS, 27.

[21]   X. Ferriol, A. G. García, R. Ochoa, I. Bravo, R. Blanco, E. Estrada et al., “Validación de un ELISA para la Cuantificación de IgG Humana Anti Proteína de Neisseria meningitidis Serogrupo B,” Revista Cubana de Medicina Tropical, Vol. 5, No. 2, 1999, pp. 99-105.

[22]   M. Nerey, R. Ochoa, J. C. Martínez, T. Licea, X. Ferriol, A. García, et al., “Validación de un ELISA para la Cuantificación de IgG Humana Anti-Polisacárido Capsular de Neisseria meningitidis Serogrupo C,” Biotecnología Aplicada, Vol. 16, No. 2, 1999, pp. 113-115.

[23]   T. Rodríguez, M. Lastre, B. Cedré, J. del Campo, G. Bracho, C. Zayas et al., “Standardization of Neisseria meningitidis Serogroup B Colorimetric Serum Bactericidal Assay,” Clinical and Diagnostic Laboratory Immunology, Vol. 9, No. 1, 2002, pp. 109-114.

[24]   H. Findlow, J. Southern, L. Mabey, P. Balmer, R. S. Heyderman, C. Auckland, et al., “Immunoglobulin G Subclass Response to a Meningococcal Quadrivalent Polysaccharide-Diphtheria Toxoid Conjugate Vaccine,” Clinical and Vaccine Immunology, Vol. 13, No. 4, 2006, pp. 507-510. doi:10.1128/CVI.13.4.507-510.2006

[25]   W. F. Reisen, F. Skvaril and D. G. Braun, “Natural Infection of Man with Group A Streptococci. Levels, Restriction in Class, Subclass and Type; and Clonal Appearance of Polysaccharide Group-Specific Antibodies,” Scandinavian Journal of Immunology, Vol. 5, No. 4, 1976, pp. 383-390.

[26]   W. J. Yount, M. M. Dorner, H. G. Kunkel and E. A. Kabat, “Studies on Human Antibodies. VI. Selected Variations in Subgroup Composition and Genetic Markers,” The Journal of Experimental Medicine, Vol. 127, No. 3, 1968, pp. 633-646. doi:10.1084/jem.127.3.633

[27]   D. J. Barrett and E, M. Ayoub, “IgG2 Subclass Restriction of Antibody to Pneumococcal Polysaccharides,” Clinical & Experimental Immunology, Vol. 63, No. 1, 1986, pp. 127-134.

[28]   M. G. Scott, D. E. Briles, P. G. Shackelford, D. S. Smith and M. H. Nahm, “Human Antibodies to Phosphocholine. IgG Anti-PC Antibodies Express Restricted Numbers of V and C Regions,” The Journal of Immunology, Vol. 138, No. 10, 1987, pp. 3325-3331.

[29]   A. Pollard, R. Galassini, E. Van der Voort, R. Booy, P. Langford, S. Nadel, et al., “Humoral Immune Responses to Neisseria meningitides in Children,” Infection and Immunity, Vol. 67, No. 5, 1999, pp. 2441-2451.

[30]   M. Broker and K. Veitch, “Quadrivalent Meningococcal Vaccines: Hyporesponsiveness as an Important Consideration When Choosing between the Use of Conjugate Vaccine or Polysaccharide Vaccine,” Travel Medicine and Infectious Disease, Vol. 8, No. 1, 2010, pp. 47-50. doi:10.1016/j.tmaid.2009.12.001

[31]   H. Keyserling, T. Papa, K. Koranyi, R. Ryall, E. Bassily, M. J. Bybel, et al., “Safety, Immunogenicity, and Immune Memory of a Novel Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine (MCV-4) in Healthy Adolescents,” Archives of Pediatrics & Adolescent Medicine, Vol. 159, No. 10, 2005, pp. 907-913. doi:10.1001/archpedi.159.10.907

[32]   K. E. Quakyi, C. E. Frasch, N. Buller and C. M. Tsai, “Immunization with Meningococcal Outer-Membrane Protein Vesicles Containing Lipooligosaccharide Protects Mice against Lethal Experimental Group B Neisseria meningitidis Infection and Septic Shock,” Journal of Infectious Diseases, Vol. 180, No. 3, 1999, pp. 747-754. doi:10.1086/314927

[33]   D. Benjamin, D. P. Hartmann, L. S. Bazar, R. J. Jacobson and M. S. Filmore, “Human B Cell Line Can Be Triggered to Secrete an Interleukin-2-Like Molecule,” Cellular Immunology, Vol. 121, No. 1, 1989, pp. 30-48. doi:10.1016/0008-8749(89)90003-8

[34]   M. Kobayashi, L. Fitz, M. Ryan, R. M. Hewick, S. C. Clark, S. Chan, et al., “Identification and Purification of Natural Killer Cell Stimulatory Factor (NSKD), a Cytokine with Multiple Biologic Effects on Human Lymphocytes,” The Journal of Experimental Medicine, Vol. 170, No. 3, 1989, pp. 827-845. doi:10.1084/jem.170.3.827

[35]   J. Mengel, L. Dare, G. M. Dare, M. Delgado, A. Nomizo, J. S. Silva, et al., “An Activated Murine B Cell Lymphoma Line Produces a Factor Like Activity Which Is Functionally Related to Human NK Cell Stimulatory Factor,” European Journal of Immunology, Vol. 22, No. 12, 1992, pp. 3137-3178. doi:10.1002/eji.1830221222

[36]   Y. Pang, Y. Norihisha, S. Benjamin, R. R. S. Kantor and H. A. Young, “IFN? Gene Expression in Human B Cell Lines: Induction by IL-2 PKC Activators and Possible Effect of Hyporesponsiveness on Gene Regulation,” Blood, Vol. 80, No. 3, 1992, pp. 724-729.

[37]   K. Kuwano, S. Arai, T. Munakata, Y. Tomita, Y. Uoshitake and K. Kumagai, “Suppressive Effects of Human NK Cells or EBV Induced Immunoglobulin Synthesis,” The Journal of Immunology, Vol. 137, No. 5, 1980, pp. 1462-1467.

[38]   R. O. Enders, E. Kuchmir, J. W. Kappler, P. Marrack and S. C. Kinsky, “A Requirement for Nonspecific T Cell Factors in Antibody Responses to ‘T Cell Independent’ Antigens,” The Journal of Immunology, Vol. 130, No. 2, 1983, pp. 781-89.

[39]   B. L. Pike and G. J. V. Nossal, “A Reappraisal of ‘T-Independent’ Antigens,” The Journal of Immunology, Vol. 132, No. 4, 1984, pp. 1687-1695.

[40]   B. L. Pike, A. Raubitschek and G. J. V. Nossal, “Human Interlekin 2 Can Promote the Growth and Differentiation of Single Hapten-Specific B Cells in the Presence of Specific Antigen,” Proceedings of the National of Academy of Sciences of the United States of America, Vol. 81, No. 24, 1984, pp. 7917-21. doi:10.1073/pnas.81.24.7917

[41]   P. M. Anderson, C. Caliguiri, T. O. Brien, T. Manley, J. Ritz and J. F. Schlossman, “Fc? Receptor Type III (CD16) Is Included in the ? NK Receptor Complex Expressed by Human NK Cells,” Proceedings of the National of Academy of Sciences of the United States of America, Vol. 87, No. 6, 1990, pp. 2274-2279. doi:10.1073/pnas.87.6.2274

[42]   C. M. Snapper, T. M. McIntyre, R. Mandler, L. M. T. Pacanha, F. D. Finkelman, A. Lees, et al., “Induction of IgG3 Secretion by IFN?: A Model for T Cell-Independent Class Switching in Response to T Cell-Independent Type 2 Antigens,” The Journal of Experimental Medicine, Vol. 175, No. 5, 1992, pp. 1367-1371. doi:10.1084/jem.175.5.1367

[43]   M. D. Snape, K. P. Perrett, K. J. Ford, T. M. John, D. Pace, L. M. Yu, J. M. Langley, S. McNeil, P. M. Dull, F. Ceddia, A. Anemona, S. A. Halperin, S. Dobson and A. J. Pollard, “Immunogenicity of a Tetravalent Meningococcal Glycoconjugate Vaccine in Infants: A Randomized Controlled Trial,” JAMA, Vol. 299, No. 2, 2008, pp. 173-84. doi:10.1001/jama.2007.29-c